The overall aim of the studies in this proposal is to determine the biological role of IgD. Investigations will focus on the possible triggering role of membrane IgD, and a proposed Fc receptor for IgD. (1) We will test the hypothesis that lymphocyte membrane IgD and IgM have a role in triggering or inhibiting differentiation of B cells to antibody secreting cells. The system used will be to determine the effects of purified antibodies to IgD and IgM on Ig production by mitogen stimulated human peripheral blood lymphocytes. Preliminary results show that anti-IgD can augment and anti-IgM can suppress Ig production in this system, and the molecular mechanisms involved in these reactions will be analyzed. To further investigate the apparent enhancing effect of anti-IgD we will test the effect of anti-IgD and anti-IgM insolubilized by covalent coupling to polyacrylamide beads, with and without added mitogen. Bacteria with specific IgD-binding activity will also be tested for their capacity to stimulate Ig secretion. (2) We will test the hypothesis that lymphocytes and/or macrophages bear Fc receptors for IgD. Preliminary data strongly suggest that a large fraction of T lymphocytes bear receptors for IgD as assessed by binding of IgD coated indicator cells. Studies will be directed at characterizing the receptor and its possible functional role. The subpopulation(s) of cells bearing the receptors will be characterized with regard to other membrane markers in particular Fc receptors for other classes, and tissue distribution. Functional analysis will include testing responses of isolated IgD-receptor bearing cells to mitogens and alloantigens. Subpopulations of cells bearing the IgD receptor will be tested for regulatory activity for pokeweed mitogen induced B cell differentiation to Ig secreting plasma cells. Preliminary studies also suggest that the IgD receptor can be induced in vitro by its ligand. This phenomenon will be further characterized with regard to mechanism and role.